Photo of Hongbo R. Luo, PhD

Hongbo R. Luo, PhD

Boston Children's Hospital

Boston Children's Hospital
Phone: (617) 919-2303
Fax: (617) 730-0885


Hongbo.Luo@childrens.harvard.edu

Photo of Hongbo R. Luo, PhD

Boston Children's Hospital
Phone: (617) 919-2303
Fax: (617) 730-0885


Hongbo.Luo@childrens.harvard.edu

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Hongbo R. Luo, PhD

Boston Children's Hospital

EDUCATIONAL TITLES

  • Professor, Pathology, Harvard Medical School
  • Professor, Pathology and Lab Medicine, Boston Children's Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

Our research focuses on signaling pathways triggered by inositol phospholipid PtdIns(3,4,5)P3, which has been implicated in various cellular processes such as proliferation, growth, apoptosis, polarity, chemotaxis and cytoskeletal rearrangement. PtdIns(3,4,5)P3 exerts its function by mediating protein translocation via binding to their pleckstrin homolog (PH)-domains. Membrane translocation of PH-domains was previously thought to be dependent solely upon concentrations of PtdIns(3,4,5)P3 in the membrane which is regulated by PI3K and PTEN. Recently, we discovered that two intracellular inositol phosphates InsP7 and Ins(1,3,4,5)P4 compete with PtdIns(3,4,5)P3 for binding to the PH domains, and thereby attenuate their membrane translocation. This result provides another level of regulation for PH domain translocation, namely relative levels of InsP7 and PtdIns(3,4,5)P3. Our lab will continue to elucidate the molecular mechanism and the physiological consequence of the inositol phosphate-mediated suppression of PtdIns(3,4,5)P3 signaling in a variety of cellular processes. #p Our lab is also interested in the role of neutrophils and innate immunity in hematopoiesis and leukemogenesis. Neutrophils in the bone marrow and circulation release various factors that can modulate hematopoiesis and myelopoiesis. We are currently exploring the role of ROS and proteases in infection-induced myelopoiesis. We are also interested in the molecular and cellular mechanisms that govern the release (mobilization) of neutrophils from the bone marrow during the course of inflammation. Similar mechanisms may also be involved in mobilization of leukemia cells.

Publications from Harvard Catalyst Profiles

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  • Yang J, Gao C, Liu M, Liu YC, Kwon J, Qi J, Tian X, Stein A, Liu YV, Kong NR, Wu Y, Yin S, Xi J, Chen Z, Kumari K, Wong H, Luo H, Silberstein LE, Thoms JAI, Unnikrishnan A, Pimanda JE, Tenen DG, Chai L. Targeting an inducible SALL4-mediated cancer vulnerability with sequential therapy. Cancer Res 2021. PubMed
  • Zhang Y, Xie X, Yeganeh PN, Lee DJ, Valle-Garcia D, Meza-Sosa KF, Junqueira C, Su J, Luo HR, Hide W, Lieberman J. Immunotherapy for breast cancer using EpCAM aptamer tumor-targeted gene knockdown. Proc Natl Acad Sci U S A 2021. PubMed
  • Kong NR, Bassal MA, Tan HK, Kurland JV, Yong KJ, Young JJ, Yang Y, Li F, Lee JD, Liu Y, Wu CS, Stein A, Luo HR, Silberstein LE, Bulyk ML, Tenen DG, Chai L. Zinc Finger Protein SALL4 Functions through an AT-Rich Motif to Regulate Gene Expression. Cell Rep 2021; 34:108574. PubMed
  • Gao J, Hou S, Yuan S, Wang Y, Gao Y, Sun X, Wang W, Chu Y, Zhou Y, Feng X, Luo HR, Cheng T, Shi J, Yuan W, Wang X. -Deficient Neutrophils Promote Hematopoietic Stem/Progenitor Cell Proliferation Mesenchymal Stem Cells. Front Cell Dev Biol 2021; 9:650599. PubMed
  • Hu JJ, Liu X, Xia S, Zhang Z, Zhang Y, Zhao J, Ruan J, Luo X, Lou X, Bai Y, Wang J, Hollingsworth LR, Magupalli VG, Zhao L, Luo HR, Kim J, Lieberman J, Wu H. FDA-approved disulfiram inhibits pyroptosis by blocking gasdermin D pore formation. Nat Immunol 2020; 21:736-745. PubMed
  • Wang Y, Sun X, Yuan S, Hou S, Guo T, Chu Y, Pang T, Luo HR, Yuan W, Wang X. Interleukin-1β inhibits normal hematopoietic expansion and promotes acute myeloid leukemia progression via the bone marrow niche. Cytotherapy 2020; 22:127-134. PubMed
  • Zhang X, Guo R, Kambara H, Ma F, Luo HR. The role of CXCR2 in acute inflammatory responses and its antagonists as anti-inflammatory therapeutics. Curr Opin Hematol 2019; 26:28-33. PubMed
  • You Y, Chen J, Zhu F, Xu Q, Han L, Gao X, Zhang X, Luo HR, Miao J, Sun X, Ren H, Du Y, Guo L, Wang X, Wang Y, Chen S, Huang N, Li J. Glutaredoxin 1 up-regulates deglutathionylation of α4 integrin and thereby restricts neutrophil mobilization from bone marrow. J Biol Chem 2018. PubMed
  • Karatepe K, Zhu H, Zhang X, Guo R, Kambara H, Loison F, Liu P, Yu H, Ren Q, Luo X, Manis J, Cheng T, Ma F, Xu Y, Luo HR. Proteinase 3 Limits the Number of Hematopoietic Stem and Progenitor Cells in Murine Bone Marrow. Stem Cell Reports 2018; 11:1092-1105. PubMed
  • Wang X, Gao Y, Gao J, Li M, Zhou M, Wang J, Pang Y, Cheng H, Yuan C, Chu Y, Jiang Y, Zhou J, Luo HR, Ju Z, Cheng T, Yuan W. Rheb1 loss leads to increased hematopoietic stem cell proliferation and myeloid-biased differentiation in vivo. Haematologica 2018. PubMed
  • Yim SH, Everley RA, Schildberg FA, Lee SG, Orsi A, Barbati ZR, Karatepe K, Fomenko DE, Tsuji PA, Luo HR, Gygi SP, Sitia R, Sharpe AH, Hatfield DL, Gladyshev VN. Role of Selenof as a Gatekeeper of Secreted Disulfide-Rich Glycoproteins. Cell Rep 2018; 23:1387-1398. PubMed
  • Zhang X, Liu P, Zhang C, Chiewchengchol D, Zhao F, Yu H, Li J, Kambara H, Luo KY, Venkataraman A, Zhou Z, Zhou W, Zhu H, Zhao L, Sakai J, Chen Y, Ho YS, Bajrami B, Xu B, Silberstein LE, Cheng T, Xu Y, Ke Y, Luo HR. Positive Regulation of Interleukin-1β Bioactivity by Physiological ROS-Mediated Cysteine S-Glutathionylation. Cell Rep 2017; 20:224-235. PubMed
  • Teng Y, Luo HR, Kambara H. Heterogeneity of neutrophil spontaneous death. Am J Hematol 2017. PubMed
  • Zhu H, Kwak HJ, Liu P, Bajrami B, Xu Y, Park SY, Nombela-Arrieta C, Mondal S, Kambara H, Yu H, Chai L, Silberstein LE, Cheng T, Luo HR. Reactive Oxygen Species-Producing Myeloid Cells Act as a Bone Marrow Niche for Sterile Inflammation-Induced Reactive Granulopoiesis. J Immunol 2017; 198:2854-2864. PubMed
  • Bajrami B, Zhu H, Kwak HJ, Mondal S, Hou Q, Geng G, Karatepe K, Zhang YC, Nombela-Arrieta C, Park SY, Loison F, Sakai J, Xu Y, Silberstein LE, Luo HR. G-CSF maintains controlled neutrophil mobilization during acute inflammation by negatively regulating CXCR2 signaling. J Exp Med 2016; 213:1999-2018. PubMed
  • Qi Q, Li DY, Luo HR, Guan KL, Ye K. Netrin-1 exerts oncogenic activities through enhancing Yes-associated protein stability. Proc Natl Acad Sci U S A 2015; 112:7255-60. PubMed
  • Kaunisto A, Henry WS, Montaser-Kouhsari L, Jaminet SC, Oh EY, Zhao L, Luo HR, Beck AH, Toker A. NFAT1 promotes intratumoral neutrophil infiltration by regulating IL8 expression in breast cancer. Mol Oncol 2015. PubMed
  • Kwak HJ, Liu P, Bajrami B, Xu Y, Park SY, Nombela-Arrieta C, Mondal S, Sun Y, Zhu H, Chai L, Silberstein LE, Cheng T, Luo HR. Myeloid cell-derived reactive oxygen species externally regulate the proliferation of myeloid progenitors in emergency granulopoiesis. Immunity 2015; 42:159-71. PubMed
  • Loison F, Zhu H, Karatepe K, Kasorn A, Liu P, Ye K, Zhou J, Cao S, Gong H, Jenne DE, Remold-O'Donnell E, Xu Y, Luo HR. Proteinase 3-dependent caspase-3 cleavage modulates neutrophil death and inflammation. J Clin Invest 2014; 124:4445-58. PubMed
  • Jo H, Loison F, Luo HR. Microtubule dynamics regulates Akt signaling via dynactin p150. Cell Signal 2014. PubMed
  • Hongbo R. Luo. A dual regulator of neutrophil recruitment Blood 2014; 123:1983.
  • Liang OD, Lu J, Nombela-Arrieta C, Zhong J, Zhao L, Pivarnik G, Mondal S, Chai L, Silberstein LE, Luo HR. Deficiency of lipid phosphatase SHIP enables long-term reconstitution of hematopoietic inductive bone marrow microenvironment. Dev Cell 2013; 25:333-49. PubMed
  • Jo H, Mondal S, Tan D, Nagata E, Takizawa S, Sharma AK, Hou Q, Shanmugasundaram K, Prasad A, Tung JK, Tejeda AO, Man H, Rigby AC, Luo HR. Small molecule-induced cytosolic activation of protein kinase Akt rescues ischemia-elicited neuronal death. Proc Natl Acad Sci U S A 2012; 109:10581-6. PubMed
  • Sakai, J., Li, J., Subramanian, K.K., Mondal, S., Bajrami, B., Hattori, H., Jia, Y., Dickinson, B.C., Zhong, J., Ye, K., Chang, C.J., Ho, Y.S., Zhou, J., and Luo, H.R. Reactive oxygen species (ROS)-induced actin glutathionylation and its modulation by glutaredoxin 1 are key physiological regulatory mechanisms controlling actin dynamics in neutrophils Immunity 2012; 37:1037-1049.
  • Jo H, Lo PK, Li Y, Loison F, Green S, Wang J, Silberstein LE, Ye K, Chen H, Luo HR. Deactivation of Akt by a small molecule inhibitor targeting pleckstrin homology domain and facilitating Akt ubiquitination. Proc Natl Acad Sci U S A 2011. PubMed
  • Prasad, A., Y. Jia, A. Chakraborty, Y. Li, S.K. Jain, J. Zhong, S.G. Roy, F. Loison, S. Mondal, J. Sakai, C. Blanchard, S.H. Snyder, and H.R. Luo. Inositol hexakisphosphate kinase 1 regulates neutrophil function in innate immunity by inhibiting phosphatidylinositol-(3,4,5)-trisphosphate signaling Nat Immunol 2011; 12:752.
  • Carbo C, Duerschmied D, Goerge T, Hattori H, Sakai J, Cifuni SM, White GC, Chrzanowska-Wodnicka M, Luo HR, Wagner DD. Integrin-independent role of CalDAG-GEFI in neutrophil chemotaxis. J Leukoc Biol 2010; 88:313-9. PubMed
  • Simarro M, Giannattasio G, De la Fuente MA, Benarafa C, Subramanian KK, Ishizawar R, Balestrieri B, Andersson EM, Luo HR, Orduña A, Boyce J, Anderson P. Fas-activated serine/threonine phosphoprotein promotes immune-mediated pulmonary inflammation. J Immunol 2010; 184:5325-32. PubMed
  • Yu H, Li Y, Gao C, Fabien L, Jia Y, Lu J, Silberstein LE, Pinkus GS, Ye K, Chai L, Luo HR. Relevant mouse model for human monocytic leukemia through Cre/lox-controlled myeloid-specific deletion of PTEN. Leukemia 2010; 24:1077-80. PubMed
  • Hattori H, Subramanian KK, Sakai J, Luo HR. Reactive oxygen species as signaling molecules in neutrophil chemotaxis. Commun Integr Biol 2010; 3:278-81. PubMed
  • Hattori H, Subramanian KK, Sakai J, Jia Y, Li Y, Porter TF, Loison F, Sarraj B, Kasorn A, Jo H, Blanchard C, Zirkle D, McDonald D, Pai SY, Serhan CN, Luo HR. Small-molecule screen identifies reactive oxygen species as key regulators of neutrophil chemotaxis. Proc Natl Acad Sci U S A 2010; 107:3546-51. PubMed
  • Xu Y, Loison F, Luo HR. Neutrophil spontaneous death is mediated by down-regulation of autocrine signaling through GPCR, PI3Kgamma, ROS, and actin. Proc Natl Acad Sci U S A 2010; 107:2950-5. PubMed
  • Jo H, Loison F, Hattori H, Silberstein LE, Yu H, Luo HR. Natural product Celastrol destabilizes tubulin heterodimer and facilitates mitotic cell death triggered by microtubule-targeting anti-cancer drugs. PLoS ONE 2010; 5:e10318. PubMed
  • Kasorn A, Alcaide P, Jia Y, Subramanian KK, Sarraj B, Li Y, Loison F, Hattori H, Silberstein LE, Luscinskas WF, Luo HR. Focal adhesion kinase regulates pathogen-killing capability and life span of neutrophils via mediating both adhesion-dependent and -independent cellular signals. J Immunol 2009; 183:1032-43. PubMed
  • Sarraj B,Massberg S,Li Y,Kasorn A,Subramanian K,Loison F,Silberstein LE,von Andrian U,Luo HR. Myeloid-specific deletion of tumor suppressor PTEN augments neutrophil transendothelial migration during inflammation. J Immunol 2009; 182:7190-200. PubMed
  • Li Y,Jia Y,Pichavant M,Loison F,Sarraj B,Kasorn A,You J,Robson BE,Umetsu DT,Mizgerd JP,Ye K,Luo HR. Targeted deletion of tumor suppressor PTEN augments neutrophil function and enhances host defense in neutropenia-associated pneumonia. Blood 2009; 113:4930-41. PubMed
  • Jia Y,Schurmans S,Luo HR. Regulation of innate immunity by inositol 1,3,4,5-tetrakisphosphate. Cell Cycle 2008; 7:2803-8. PubMed
  • Jo H, Jia Y, Subramanian KK, Hattori H, Luo HR. Cancer Cell-Derived Clusterin Modulates the PI3K-Akt Pathway through Attenuation of IGF-1 during Serum Deprivation. Mol Cell Biol 2008; 28:4285-99. PubMed
  • Luo HR, Loison F. Constitutive neutrophil apoptosis: mechanisms and regulation. Am J Hematol 2008; 83:288-95. PubMed
  • Liu Z, Jang SW, Liu X, Cheng D, Peng J, Yepes M, Li XJ, Matthews S, Watts C, Asano M, Hara-Nishimura I, Luo HR, Ye K. Neuroprotective actions of PIKE-L by inhibition of SET proteolytic degradation by asparagine endopeptidase. Mol Cell 2008; 29:665-78. PubMed
  • Jia Y, Loison F, Hattori H, Li Y, Erneux C, Park SY, Gao C, Chai L, Silberstein LE, Schurmans S, Luo HR. Inositol trisphosphate 3-kinase B (InsP3KB) as a physiological modulator of myelopoiesis. Proc Natl Acad Sci U S A 2008; 105:4739-44. PubMed
  • Le Y, Zhu BM, Harley B, Park SY, Kobayashi T, Manis JP, Luo HR, Yoshimura A, Hennighausen L, Silberstein LE. SOCS3 protein developmentally regulates the chemokine receptor CXCR4-FAK signaling pathway during B lymphopoiesis. Immunity 2007; 27:811-23. PubMed
  • Jia Y, Subramanian KK, Erneux C, Pouillon V, Hattori H, Jo H, You J, Zhu D, Schurmans S, Luo HR. Inositol 1,3,4,5-tetrakisphosphate negatively regulates phosphatidylinositol-3,4,5- trisphosphate signaling in neutrophils. Immunity 2007; 27:453-67. PubMed
  • Marechal Y, Pesesse X, Jia Y, Pouillon V, Perez-Morga D, Daniel J, Izui S, Cullen PJ, Leo O, Luo HR, Erneux C, Schurmans S. Inositol 1,3,4,5-tetrakisphosphate controls proapoptotic Bim gene expression and survival in B cells. Proc Natl Acad Sci U S A 2007; 104:13978-83. PubMed
  • Hattori H, Zhang X, Jia Y, Subramanian KK, Jo H, Loison F, Newburger PE, Luo HR. RNAi screen identifies UBE2D3 as a mediator of all-trans retinoic acid-induced cell growth arrest in human acute promyelocytic NB4 cells. Blood 2007; 110:640-50. PubMed
  • Fabien Loison1,2, Haiyan Zhu3, Kutay Karatepe1, Anongnard Kasorn1.4, Peng Liu3, Keqiang Ye5, Dieter E. Jenne6, Eileen Remold-O’Donnell7, Yuanfu Xu3, Hongbo R. Luo. Regulation of neutrophil death and inflammation by Proteinase 3 J Clin Invest .
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* Concepts are MeSH terms, automatically derived from member publications

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